| First Author | Aly S | Year | 2009 |
| Journal | J Cell Mol Med | Volume | 13 |
| Issue | 8B | Pages | 2069-82 |
| PubMed ID | 18705699 | Mgi Jnum | J:356552 |
| Mgi Id | MGI:7762644 | Doi | 10.1111/j.1582-4934.2008.00470.x |
| Citation | Aly S, et al. (2009) Mycobacteria-induced granuloma necrosis depends on IRF-1. J Cell Mol Med 13(8B):2069-2082 |
| abstractText | In a mouse model of mycobacteria-induced immunopathology, wild-type C57BL/6 (WT), IL-18-knockout (KO) and IFN-alphabeta receptor-KO mice developed circumscript, centrally necrotizing granulomatous lesions in response to aerosol infection with M. avium, whereas mice deficient in the IFN-gamma receptor, STAT-1 or IRF-1 did not exhibit granuloma necrosis. Comparative, microarray-based gene expression analysis in the lungs of infected WT and IRF-1-KO mice identified a set of genes whose differential regulation was closely associated with granuloma necrosis, among them cathepsin K, cystatin F and matrix metalloprotease 10. Further microarray-based comparison of gene expression in the lungs of infected WT, IFN-gamma-KO and IRF-1-KO mice revealed four distinct clusters of genes with variable dependence on the presence of IFN-gamma, IRF-1 or both. In particular, IRF-1 appeared to be directly involved in the differentiation of a type I immune response to mycobacterial infection. In summary, IRF-1, rather than being a mere transcription factor downstream of IFN-gamma, may be a master regulator of mycobacteria-induced immunopathology. |
